Catalytic cross-coupling reaction of esters with organoboron compounds and decarbonylative reduction of esters with HCOONH4: A new route to acyl transition metal complexes through the cleavage of acyl-oxygen bonds in esters

Article abstract of DOI:10.1021/jo0492719

The Ru₃(CO)₁₂-catalyed cross-coupling reaction of esters with organoboron compounds leading to ketones is described. A wide variety of functional groups can be tolerated under the reaction conditions. Aromatic boronates function as a coupling partner to give aryl ketones. Acyl-alkyl coupling to dialkyl ketones is also achieved by the use of 9-alkyl-9-BBN in place of boronates. The Ru₃(CO)₁₂- catalyzed decarbonylative reduction of esters with ammonium formate (HCOONH ₄) leading to hydrocarbons is also described. No expected aldehydes are produced, and controlled experiments indicate that aldehydes are not intermediate for the transformation. A hydrosilane can also be used as a reducing reagent in place of HCOONH₄. A wide variety of functional groups are compatible for both reactions. The key step for both catalytic reactions is the directing group-promoted cleavage of an acyl carbon-oxygen bond in esters, leading to the generation of acyl transition metal alkoxo complexes.

Full text of DOI:10.1021/jo0492719

Ca ta lytic Cr oss-Cou p lin g Rea ction of Ester s w ith Or ga n obor on
Com p ou n d s a n d Deca r bon yla tive Red u ction of Ester s w ith
HCOONH4: A New Rou te to Acyl Tr a n sition Meta l Com p lexes
th r ou gh th e Clea va ge of Acyl-Oxygen Bon d s in Ester s
Hiroto Tatamidani, Kazuhiko Yokota, Fumitoshi Kakiuchi, and Naoto Chatani*
Department of Applied Chemistry, Faculty of Engineering, Osaka University,
Suita, Osaka 565-0871, J apan
chatani@chem.eng.osaka-u.ac.jp
Received April 30, 2004
The Ru3(CO)12-catalyed cross-coupling reaction of esters with organoboron compounds leading to
ketones is described. A wide variety of functional groups can be tolerated under the reaction
conditions. Aromatic boronates function as a coupling partner to give aryl ketones. Acyl-alkyl
coupling to dialkyl ketones is also achieved by the use of 9-alkyl-9-BBN in place of boronates. The
Ru3(CO)12-catalyzed decarbonylative reduction of esters with ammonium formate (HCOONH4)
leading to hydrocarbons is also described. No expected aldehydes are produced, and controlled
experiments indicate that aldehydes are not intermediate for the transformation. A hydrosilane
can also be used as a reducing reagent in place of HCOONH4. A wide variety of functional groups
are compatible for both reactions. The key step for both catalytic reactions is the directing group-
promoted cleavage of an acyl carbon-oxygen bond in esters, leading to the generation of acyl
transition metal alkoxo complexes.
SCHEME 1. Gen er a tion of Acyl Tr a n sition Meta l
Com p lexes
In tr od u ction
Acyl transition metal complexes are ubiquitous in
organometallic chemistry, and serve as important metal-
lic species for a variety of transition metal-catalyzed
reactions.1 A variety of methods are available for gener-
ating acyl transition metal complexes (Scheme 1). The
insertion of CO into a carbon-metal bond in alkyl, aryl,
or vinyl transition metal complexes, which are formed
via the hydrometalation or carbometalation of alkenes
(or alkynes), the oxidative addition of halides (or pseudo
halides), and so on, all generate acyl transition metal
complexes. The oxidative addition of various carbonyl
compounds, such as aldehydes, acid halides, acid anhy-
drides, and thioesters, is another candidate to generate
acyl complexes. Many catalytic and stoichiometric studies
have been conducted,2 but fewer studies have been
conducted on the oxidative addition of acyl carbon-
oxygen bonds in esters to transition metal complexes.3
The example of the oxidative addition of acyl-O bonds
in esters is very rare because the alkoxy group is not a
good leaving group. Yamamoto reported that phenyl
acetate adds oxidatively to Ni(cod)2/bipyridine to give a
methylnickel phenoxide complex, which is formed by
decarbonylation of the intermediate acetylnickel com-
plex.4 Other complexes, such as Ni(cod)2/PPh3,4 Mo(N2)2-
(dppe)2,5 HRh(PPh3)4,6 Ru(CO)2(PPh3)3,7 and Cp*RhCl-
(mdmpp-κP,κO),8 have also been found to cleave acyl-O
bonds of esters, with the ester carbonyl group being
ultimately converted to a metal-coordinated CO ligand.
(1) Collman, J . P.; Hegedus, L. S.; Norton, J . R.; Finke, R. G.
Principles and Applications of Organotransition Metal Chemistry;
University Science Books: Mill Valley, CA, 1987. Spessard, G. O.;
Miessler, G. L. Organometallic Chemistry; Prentice Hall: Upper Saddle
River, NJ , 1996. Tsuji, J . Transition Metal Reagents and Catalysts;
Wiley: Chichester, U.K., 2000.
(4) Yamamoto, T.; Ishizu, J .; Kohara, T.; Komiya, S.; Yamamoto,
A. J . Am. Chem. Soc. 1980, 102, 3758.
(5) Tatsumi, T.; Tominaga, H.; Hidai, M.; Uchida, Y. J . Organomet.
Chem. 1981, 218, 177.
(6) Yamamoto, T.; Miyashita, S.; Naito, Y.; Komiya, S.; Ito, T.;
Yamamoto, A. Organometallics 1982, 1, 808.
(7) Hiraki, K.; Kira, S.; Kawano, H. Bull. Chem. Soc. J pn. 1997,
70, 1583.
(8) Yamamoto, Y.; Han, X.-H.; Ma, J .-F. Angew. Chem., Int. Ed.
2000, 39, 1965.
(2) Zapf, A. Angew. Chem., Int. Ed. 2003, 42, 5394.
(3) For recent reviews on the cleavage of ester bonds, see: Lin, Y.-
S.; Yamamoto, A. In Activation of Unreactive Bonds and Organic
Synthesis; Murai, S., Ed.; Springer: Berlin, Germany, 1999; pp 161-
192. Yamamoto, A. Adv. Organomet. Chem. 1992, 34, 111.
10.1021/jo0492719 CCC: $27.50 © 2004 American Chemical Society
Published on Web 07/23/2004
J . Org. Chem. 2004, 69, 5615-5621
5615

Tatamidani et al.
SCHEME 2. Ou r Str a tegy to Gen er a te of Acyl
Grotjahn isolated an acyl rhodium complex from the
reaction of an aryl acetate containing a phosphine moiety
with a Rh(I) complex.9 Yamamoto also isolated (aryloxo)-
(trifluoroacetyl)palladium complexes, produced by the
oxidative addition of aryl trifluoroacetates to Pd(0) under
mild conditions.10 To the best of our knowledge, only two
catalytic reactions, which involve the cleavage of acyl-O
bonds in esters, are known. Yamamoto reported on the
Pd-catalyzed coupling reaction of aryl trifluoroacetates
with arylboronic acids under relatively mild reaction
conditions, leading to aryl trifluoromethyl ketones.11
Gooâen found that the Mizoroki-Heck-type reaction of
esters proceeds when p-nitrophenyl or pentafluorophenyl
esters are employed.12 All esters that are used for the
catalytic cleavage of acyl-O bonds in esters are elec-
tronically activated by the presence of an electron-
withdrawing group at the carboxylic or alcoholic moiety.
Com p lexes
Resu lts a n d Discu ssion
Cr oss-Cou plin g Reaction with Or gan obor on Com -
p ou n d s. The cleavage of acyl-O bonds in esters could
lead to acyl alkoxo transition metal species, as shown in
Scheme 2. It is well-known that alkoxo or hydroxo
transition metal species are much more reactive with
respect to the transmetalation of organoboron reagents.17,18
We then focused our initial efforts on cross-coupling
reactions of esters with organoboron compounds. 3-Phen-
ylpropionic acid 2-pyridinylmethyl ester (1) and PhB-
(OCH2CH2O) (2a ) were selected as the first substrate and
reagent for screening a broad spectrum of transition
metal complexes. Among the various transition metal
complexes examined, only Ru3(CO)12 showed a catalytic
activity for eq 1. The reaction of 1 (1 mmol) and
The reactivity of acyl transition metal complexes could
be changed or controlled by the nature of the Y group on
the metal (Scheme 1). However, little is known concern-
ing the reactivity of acyl alkoxo complexes (Y ) OR′)
because no appropriate method for their generation has
been reported, as described above. The cleavage of an
acyl-O bond in esters represents a good candidate for
use in generating acyl alkoxo complexes. Our strategy
for generating acyl transition metal complexes directly
from esters is based on the accepted dogma that hetero-
atom-directing groups promote the cleavage of unreactive
bonds. We have previously reported on catalytic reactions
which involve the facile cleavage of C-H,13 C-C,14 C-F,15
and C-O bonds16 by taking advantage of the coordination
of the directing group on the transition metals. The
coordination of a carbonyl oxygen or sp2-nitorogen to
transition metals is a key step in these catalytic reac-
tions. We subsequently chose 2-pyridylmethyl esters as
the substrate for generating acyl alkoxo complexes. The
coordination of the pyridine nitrogen in the ester would
be expected to facilitate the cleavage of acyl-O bonds in
esters, as shown in Scheme 2. Most importantly, various
combinations of catalysts and directing groups would be
available, suggesting the possibility of generating a wide
variety of acyl alkoxo transition metal complexes. Our
purpose is to provide new catalytic reactions based on a
new method for the generation of acyl alkoxo transition
metal complexes. We wish to report herein on some new
transformations of Ru3(CO)12-catalyzed reaction of esters
involving the cleavage of acyl-O bonds: (i) cross-coupling
reactions with organoboron compounds and (ii) decarbo-
nylative reductions with HCOONH4.
phenylboronate 2a (1.5 mmol) in the presence of Ru3-
(CO)12 (0.03 mmol) in toluene (3 mL) at 160 °C for 20 h
in a 9-mL sealed tube gave 1,3-diphenylpropan-1-one (3a )
and its branched isomer in 71% GC yield in a ratio of
94:6. In addition, benzophenone, which was formed by
the reaction of 2a with Ru3(CO)12, was produced in <5%
yield. The corresponding benzyl ester failed to react,
indicating that the presence of nitrogen in the substrate
is essential for the reaction to proceed. Of the solvents
examined, toluene was the best (chlorobenzene 63%,
dioxane 58%, DMF 48%, CH3CN 34%). The use of a CO
atmosphere had no effect on the efficiency of the reaction
(67%, n:i ) 97:3). Some phenyl donors, such as PhB(OH)2
(11%), PhB(OCH2CH2CH2O) (68%), PhB(OCH2CMe2-
CH2O) (67%), and NaBPh4 (11%), were screened, and we
rapidly discovered that 2a was a superior phenyl donor,
resulting in the highest yield of 3a . Lowering the reaction
temperature (120 °C) slightly improved both the yield to
83% isolated yield (86% GC yield) and the ratio (n:i )
99:1), as shown in entry 1 of Table 1.
(9) Grotjahn, D. B.; J oubran, C. Organometallics 1995, 14, 5171.
(10) Nagayama, K.; Shimizu, I.; Yamamoto, A. Bull. Chem. Soc. J pn.
1999, 72, 799.
(11) Kakino, R.; Shimizu, I.; Yamamoto, A. Bull. Chem. Soc. J pn.
2001, 74, 371.
(12) Gooâen, L. J .; Paetzold, J . Angew. Chem., Int. Ed. 2002, 41,
1237.
(13) Kakiuchi, F.; Murai, S. Acc. Chem. Res. 2002, 35, 826. Kakiuchi,
F.; Chatani, N. Adv. Synth. Catal. 2003, 345, 1077. Asaumi, T.;
Chatani, N.; Matsuo, T.; Kakiuchi, F.; Murai, S. J . Org. Chem. 2003,
68, 7538 and references therein.
As expected from the results of the Suzuki-Miyaura
coupling reaction,17 various functional groups, such as
ethers, halides, ketones, and esters, were compatible with
the cross-coupling reaction (Table 1). The presence of a
(14) Chatani, N.; Ie, Y.; Kakiuchi, F.; Murai, S. J . Am. Chem. Soc.
1999, 121, 8645.
(15) Ishii, Y.; Chatani, N.; Yorimitsu, S.; Murai, S. Chem. Lett. 1998,
157.
(16) Kakiuchi, F.; Usui, M.; Ueno, S.; Chatani, N.; Murai, S. J . Am.
Chem. Soc. 2004, 126, 2706.
(17) For reviews on the Suzuki-Miyaura coupling, see: Miyaura,
N.; Suzuki, A. Chem. Rev. 1995, 95, 2457. Miyaura, N. J . Organomet.
Chem. 2002, 653, 54. Kohta, S.; Lahirir, K.; Kashinath, D. Tetrahedron
2002, 58, 9633.
(18) Fagnou, K.; Lautens, M. Chem. Rev. 2003, 103, 169.
5616 J . Org. Chem., Vol. 69, No. 17, 2004

Acyl Transition Metal Complexes
TABLE 1. Ru 3(CO)12-Ca ta lyzed Cou p lin g Rea ction of
Ester s w ith P h en ylbor on ic Ester 2a a
It was found that the electronic nature of aryl bor-
onates has a significant effect on the efficiency of the
reaction and the ratio of normal to branched isomers (eq
4). To compare the reactivity of aryl boronates, the
reactions were carried out under the same reaction
conditions (condition A, see the footnote in Table 1) in
all cases. The reaction of 1 with 2b gave the correspond-
ing ketone 3b in high yield with complete normal
selectivity. The substitution of a methoxy group, as in
2c, also resulted in a high yield and a high ratio. On the
other hand, an aryl boronate containing an electron-
withdrawing group, as in 2f and 2g, gave the correspond-
ing products in relatively low yields with low n:i ratios.
We next examined the electronic effects of a substitu-
ent on benzoates (eq 5). Curiously, the substitution of an
electron-donating group on the phenyl ring resulted in
no reaction, in sharp contrast to an electron-withdrawing
group, such as CF3, which gave the corresponding diaryl
ketones 16 in good yields.
a
b
R ) 2-pyridinylmethyl. Reaction conditions A: ester (1
mmol), 2 (1.5 mmol) and Ru3(CO)12 (0.03 mmol) in toluene (3 mL)
at 140 °C for 20 h. c Reaction conditions B: for 40 h, otherwise
d
the same reaction conditions as reaction condition A. Reaction
conditions C: ester (1 mmol), 2 (1.5 mmol), and Ru3(CO)12 (0.03
mmol) in toluene (1 mL) at 120 °C for 40 h.
Next, our attention was directed to the coupling with
alkyl boronates. However, no reaction took place when
butylboronate, BuB(OCH2CH2O), was used as a coupling
reagent under various reaction conditions. Finally, we
found that a benzyl group can be coupled with esters 18
to give 19 when 9-benzyl-9-BBN is used as a coupling
reagent (Scheme 3). Encouraged by this result, attention
was directed toward the coupling of esters with 9-alkyl-
9-BBN, which are easily prepared by the hydroboration
of alkenes with 9-BBN. In recent years, a great deal of
progress has been made in the development of cross-
bulky substituent led to a slight decrease in product yield
(entry 4). The result in entry 9 again shows that the
presence of a pyridine ring appears to be essential for
the reaction to proceed. The reaction was also applicable
to the ferrocene ring.
A pyridine ring is not only a directing group, but an
oxazoline ring also can be used as the directing group
(eq 2). However, an sp3 nitrogen, as in 15, does not serve
as a directing group (eq 3).
J . Org. Chem, Vol. 69, No. 17, 2004 5617

Tatamidani et al.
SCHEME 4. A P r op osed Rea ction Mech a n ism
SCHEME 3. Cou p lin g w ith 9-Alk yl-9-BBN
coupling reactions of activated carboxylic acid derivatives,
such as acid chlorides,19 anhydrides,20 thioesters,21 and
others22 with organoboron reagents leading to ketones.
While most of the reactions reported thus far have been
directed to the preparation of diaryl ketones via aryloyl-
aryl coupling, using aromatic acid derivatives and aro-
matic boron compounds, only one example of aliphatic
acyl-alkyl coupling exists, to the best of our knowl-
edge.19e,23 While the results shown in Scheme 3 did not
reach a satisfactory synthetic level at the present time,
these are rare examples of a dialkyl ketone synthesis via
acyl-alkyl coupling with alkyl organoboron compounds.
An intramolecular coupling with 25 resulted in cy-
clization to give 2-phenylcyclopentanone 26 (eq 6).
28. The ruthenium in 28 attacks the ester-carbonyl group
to give the tetrahedral intermediate 29. C-O bond
cleavage takes place to afford an acyl alkoxo ruthenium
complex 30.24 The transmetalation of species 30 with a
boron compound followed by reductive elimination gives
a ketone and a regenerated ruthenium. A branched
isomer is formed from 30 or 31 via the decarbonylation/
â-hydride elimination/reinsertion/CO insertion leading to
a branched acyl ruthenium complex, which reacts with
a boron compound to give a branched isomer. While the
presence of inorganic bases is essential in reactions with
organoboron compounds,17,18 the present reaction does not
require the bases because of the direct generation of
alkoxo complexes from the cleavage of an acyl-O bond
in esters.
The ratio of normal and branched isomers parallels the
nucleophilicity of aryl boronates, as shown in eq 4. When
an electron-rich aryl boronate, such as 2b and 2c, was
used, no branched isomers were produced. On the other
hand, the use of electron-poor aryl boronates, such as 2f
and 2g, decreased the n:i ratio to 8:2. These results can
be rationalized by assuming that the more nucleophilic
R′ group on the ruthenium in 31 readily attacks the
carbon of the ruthenium-bound acyl ligand to give 32,
the C-Ru bond of which is then cleaved, forming the final
product (Scheme 4).25 This mechanism is unusual for a
concerted reductive elimination, but is similar to that
proposed for the reductive elimination of C-O from
palladium complexes proposed by Buchwald26 and
Hartwig.27 The results obtained from eq 5 also support
the above proposal. When R is 4-CF3C6H4, the nucleo-
philic attack of R′ on the acyl carbon in 31 would be
facilitated because of its electron-withdrawing nature. On
The proposed mechanism is shown in Scheme 4.
Although our efforts, which were directed toward the
isolation of the acyl alkoxo complex 30, were in vain, we
propose the intermediacy of the acyl ruthenium species
30. The coordination of the nitrogen in 27 to Ru gives
(19) For recent papers on cross-coupling reactions of acid chlorides
with organoboron compounds, see: (a) Cho, C. S.; Itotani, K.; Uemura,
S. J . Organomet. Chem. 1993, 443, 253. (b) Bumagin, N. A.; Bykov, V.
V. Tetrahedron 1997, 53, 14437. (c) Bumagin, N. A.; Korolev, D. N.
Tetrahedron Lett. 1999, 40, 3057. (d) Haddach, M.; McCarthy, J . R.
Tetrahedron Lett. 1999, 49, 3109. (e) Kabalka, G. W.; Malladi, R. R.;
Tejedor, D.; Kelley, S. Tetrahedron Lett. 2000, 41, 999. (f) Chen, H.;
Deng, M.-Z. Org. Lett. 2000, 2, 1649. (g) Wang, J .-X.; Wei, B.; Hu, Y.;
Liu, Z.; Yang, Y. Synth. Commun. 2001, 31, 3885. (h) Urawa, Y.; Ogura,
K. Tetrahedron Lett. 2003, 44, 271. (i) Urakawa, Y.; Nishiura, K.;
Souda, S.; Ogura, K. Synthesis 2003, 2882.
(20) For recent papers on cross-coupling reactions of acid anhydrides
with organoboron compounds, see: (a) Gooâen, L. J .; Ghosh, K. Angew.
Chem., Int. Ed. 2001, 40, 3458. (b) Frost, C. G.; Wadsworth, K. J . Chem.
Commun. 2001, 2316. (c) Kakino, R.; Narahashi, H.; Shimizu, I.;
Yamamoto, A. Chem. Lett. 2001, 1242. (d) Kakino, R.; Yasumi, S.;
Shimizu, I.; Yamamoto, A. Bull. Chem. Soc. J pn. 2002, 75, 137. (e)
Oguma, K.; Miura, M.; Satoh, T.; Nomura, M. J . Organomet. Chem.
2002, 648, 297. (f) Kakino, R.; Narahashi, H.; Shimizu, I.; Yamamoto,
A. Bull. Chem. Soc. J pn. 2002, 75, 1333. (g) Gooâen, L. J .; Winkle, L.;
Do¨hring, A.; Ghosh, K.; Paetgold, J . Synlett 2002, 1237. (h) Yamamoto,
A.; Kakino, R.; Shimizu, I. Helv. Chim. Acta 2001, 84, 2996. (i) Gooâen,
L. J .; Ghosh, K. Eur. J . Org. Chem. 2002, 3254.
(21) For recent papers on cross-coupling reactions of thioesters with
organoboron compounds, see: (a) Zeysing, B.; Gosch, C.; Terfort, A.
Org. Lett. 2000, 2, 1843. (b) Savarin, C.; Srogl, J .; Liebeskind, L. S.
Org. Lett. 2000, 2, 3229. (c) Liebeskind, L. S.; Srogl, J . J . Am. Chem.
Soc. 2000, 122, 11260. (d) Yu, Y.; Liebeskind, L. S. J . Org. Chem. 2004,
69, 3554.
(23) Gooâen described that alkylboronic acids were not converted
under any of the given conditions. See ref 20b. A cross-coupling reaction
of cyclopropylboronic acids with acid chlorides was achieved by the
use of palladium complexes and base. See ref 20a. While we were
preparing the paper, Liebeskind reported the coupling reaction of
aliphatic thioesters with alkyl-(9-BBN) in the presence of a stoichio-
metric amount of copper(I) thiophene-2-carboxylate and palladium
catalyst. See ref 21d.
(24) Ko, S.; Lee, C.; Choi, M.-G.; Na, Y.; Chang, S. J . Org. Chem.
2003, 68, 1607.
(25) The positive F values were observed in the Pd-catalyzed cross-
coupling reaction of in situ generated acid anhydrides with arylboronic
acids, indicating that arylboronic acids bearing an electron-withdraw-
ing group react faster than those having a more electron-donating
group. See ref 20f.
(26) Widenhoefer, R. A.; Buchwald, S. L. J . Am. Chem. Soc. 1998,
120, 6504.
(22) Gooâen, L. J .; Ghosh, K. J . Chem. Commun. 2001, 2084.
(27) Hartwig, J . F. Acc. Chem. Res. 1998, 31, 852.
5618 J . Org. Chem., Vol. 69, No. 17, 2004

Acyl Transition Metal Complexes
the other hand, when R is 4-MeOC6H4, the nucleophilic
attack of R′ would be retarded because of the electron-
donating nature of the methoxy group.
2-pyridinylethyl 36 or 2-pyridinyl ester 37 did not give
34. Other directing groups such as sp3 nitrogen, as in
15, did not function as a directing group in the reaction
with HCOONH4.
The present reaction represents a new method for the
direct synthesis of unsymmetrical ketones from esters.
Although various carboxylic acid derivatives, such as acid
chlorides, anhydrides, thioesters, and related groups,
were utilized as the substrates for the coupling reac-
tion,19-22 catalytic coupling reactions of esters are rare.11
Although some issues remain to be solved, such as the
effect of higher reaction temperatures and the formation
of branched isomers, the present work provides a rare
example of a dialkyl ketone synthesis via an aliphatic
acyl-alkyl coupling with use of alkyl boron com-
pounds.19e,28 A wide variety of functional groups can be
tolerated in the reaction even under relatively severe
reaction conditions
The use of other hydrogenation reagents, such as
HCOONa (26%) and i-PrOH (0%), was not effective;
however, HSiPh3 was also found to function as the
hydrogenation reagent to afford naphthalene (eq 8). This
reaction also gave no aldehyde.
Deca r b on yla t ive R ed u ct ion w it h HCOONH 4. In
the course of screening various combinations of catalysts
and nucleophiles in coupling reactions of esters, we found
a clean but an unexpected reaction, as shown in eq 7.29
We expected that the reaction of the 2-pyridylmethyl
ester with a hydride donor would give naphthalenecar-
baldehyde, analogous to the Rosenmund-type reduc-
tion.30,31 However, the reaction of naphthalene-2-carbox-
ylic acid pyridin-2-ylmethyl ester (33) with ammonium
formate, HCOONH4, in the presence of Ru3(CO)12 as the
catalyst, instead, resulted in decarbonylative reduction
to give naphthalene (34) in good yield and the expected
product, naphthalenecarbaldehyde, was not formed.
This method was quite compatible with various func-
tional groups, such as methoxy, chloro, fluoro, acetal,
sulfonate, ester, imido, protected amine, and even a free
amine, as shown in Table 2. Electron-donating or -with-
drawing groups on a benzene ring had no appreciable
affect on the reaction. However, the reaction of a 4-nitro
ester, such as 38f, resulted in the reduction of the nitro
group to give 2-pyridylmethyl 4-aminobenzoate in 27%
yield with no nitrobenzene 39f detected. An ester group
(COOMe) at the 4-position of the phenyl ring, as in 38k ,
was tolerated. On the other hand, the use of a cyano-
substituted ester, such as 37h , resulted in a low yield of
benzonitrile 39h because 39h also was reduced by
HCOONH4 under the reaction conditions employed. In
fact, the reaction of 2-naphthalenecarbonitrile under
identical reaction conditions gives 2-methylnaphthalene
in 27% yield and unidentified products. A keto function-
ality also did not survive under the reaction conditions,
as in 38r . Steric bulkiness around the carbonyl group,
as in 38b, led to a low conversion. The reaction is not
limited to a benzene ring system, but it is applicable to
a pyridine ring as well. The reaction of 38t gave indole
(39t) in 23% yield, but changing solvent to toluene
increased the product yield to 70%. The reaction of
ferrocenecarboxylic ester 38v gave ferrocene (39s) in 56%
yield.
The reaction of 33 (0.2 mmol) with HCOONH4 (0.6
mmol) in the presence of Ru3(CO)12 (0.01 mmol) in toluene
(0.6 mL) at 160 °C for 40 h gave naphthalene (34) in 55%
1
GC yield, along with 17% of unreacted 33 (eq 7). The H
NMR spectrum indicated that 2-pyridylmethanol is
formed in a yield comparable to that of 34. The use of
dioxane as the solvent improved the yield to 95%. Of the
solvents examined, dioxane was the solvent of choice,
although the type of solvent had no significant effect on
the yield of 34 (anisole 68%, p-xylene 51%, PrCN 71%,
CH3CONMe2 84%). When the reaction was carried out
even at 1 atm of CO, no reaction took place. Lowering
the reaction temperature decreased the yields (68% yield
at 140 °C, 14% at 120 °C). The corresponding benzyl ester
35 did not react with HCOONH4, indicating that the
presence of a nitrogen in the substrate is essential for
the reaction to proceed. It was also found that the tether
of the alcohol moiety is important. Thus, the use of
It was found that aliphatic esters 40a , 40b, and 40c
give ethylbenzenes in good yields. A steric bulkiness
around a carbonyl group retarded the reaction. Thus, the
reaction of 40e resulted in no reaction. Adamantanecar-
boxylate 40f also did not give the expected adamantane,
although it works well as the substrate in cross-coupling
reactions with the phenyl boron compound 2a , as shown
in Table 1.
(28) Carbonylative cross-coupling with 9-alkyl-9-BBN was reported.
Wakita, Y.; Yasunaga, T.; Akita, M.; Kojima, M. J . Organomet. Chem.
1986, 301, C17. Ishiyama, T.; Miyaura, N.; Suzuki, A. Tetrahedron
Lett. 1991, 32, 6923.
(29) A preliminary report has been communicated. Chatani, N.;
Tatamidani, H.; Ie, Y.; Kakiuchi, F.; Murai, S. J . Am. Chem. Soc. 2001,
123, 4849.
(30) For a review on the Rosenmund reduction, see: Mosettig, E.;
Mozingo, R. Org. React. 1948, 4, 362. For a recent paper, see: Grushin,
V. V.; Alper, H. J . Org. Chem. 1991, 56, 5159.
(31) Nagayama, K.; Kawataka, F.; Sakamoto, M.; Shimizu, I.;
Yamamoto, A. Bull. Chem. Soc. J pn. 1999, 72, 799.
The reaction was not limited to esters, in which a
2-pyridylmethyl group is attached as the directing group
at the alcohol moiety in the substrates (Table 4). The
results, as listed in Tables 1-4, show the apparent
potential utility of this transformation in terms of its
application to organic synthesis.
The proposed reaction mechanism is essentially the
same as that for the cross-coupling reaction shown in
Scheme 3, except for accompanying decarbonylation
J . Org. Chem, Vol. 69, No. 17, 2004 5619

Tatamidani et al.
TABLE 2. Red u ctive Deca r bon yla tion of Ar om a tic
Ester s Lea d in g to Ar en esa ,c
TABLE 3. Th e Ru 3(CO)12-Ca ta lyzed Rea ction of Ester s
a
w ith HCOONH4
a
Reaction conditions: ester (0.2 mmol), HCOONH4 (0.6 mmol),
and dioxane (0.6 mL) at 160 °C for 20 h.
TABLE 4. Th e Ru 3(CO)12-Ca ta lyzed Rea ction of Ester s
a
w ith HCOONH4
a
Reaction conditions: ester (0.2 mmol), HCOONH4 (0.6 mmol),
and toluene (0.6 mL) at 160 °C for 20 h.
A considerable difference in the electronic effects of the
substituent on aromatic esters was observed for the two
reactions. As shown in eq 4, the electronic nature of the
substituents had a significant effect on the reactivity in
the cross-coupling reaction. Thus, an electron-donating
group, such as a methoxy group, inhibited the coupling
reaction with phenyl boronate, in sharp contrast to a CF3
group, which gave the corresponding ketone in a good
yield. On the other hand, the decarbonylative reduction
reaction was not significantly affected by the electronic
nature of a substituent on the benzene ring, but the
substitution of an electron-donating group on the benzene
ring makes the reaction slightly more efficient than
a
Toluene was used as the solvent in place of dioxane. b See text.
c Reaction conditions: ester (0.2 mmol), HCOONH4 (0.6 mmol),
and dioxane (0.6 mL) at 160 °C for 20 h.
(Scheme 5). Decarbonylation took place in the reaction
with HCOONH4, but not in the cross-coupling reaction
with organoboron compounds. In contrast to organoboron
compounds, HCOO- (or H-) does not allow ligand ex-
change (transmetalation) to proceed efficiently with
respect to 30. The low reactivity of HCOONH4 toward
30 is responsible for the facile decarbonylation.
5620 J . Org. Chem., Vol. 69, No. 17, 2004

Acyl Transition Metal Complexes
SCHEME 5. A P r op osed Rea ction Mech a n ism
along with a 7% GC yield of 2-naphthalenemethanol
(determined as a silyl ether) and a 61% yield of 2-meth-
ylnaphthalene. Treatment of a mixture of 33 and 2-py-
ridylmethyl 3,4,5-trimethoxybenzoate (37i) with HCO-
ONH4 under identical conditions gave a 91% recovered
yield of 37i and 2-naphthalenemethanol (45% GC yield).
The expected 1,2,3-trimethoxybenzene (38i) was obtained
in trace amounts, and naphthalene and 2-methylnaph-
thalene were not detected by GC. These results show that
the present decarbonylative reduction does not involve
an aldehyde intermediate and that the formation of
aldehyde inhibits the reaction.
The present reaction represents a new type of decar-
bonylative reduction in which esters can be directly
converted to hydrocarbons, similar to the decarbonylation
of aldehydes, a reaction that is frequently employed in
organic synthesis.32 In addition, a wide variety of func-
tional groups can be tolerated in the reaction.
SCHEME 6
Su m m a r y
A new approach for generating acyl alkoxo transition
metal complexes starting from esters by taking advan-
tage of the coordination of sp2 nitrogen to ruthenium is
described. Two catalytic reactions were explored on the
basis of the methodology:33 a cross-coupling reaction with
organoboron compounds and a decarbonylative reduction
with HCOONH4 (or a hydrosilane). Further investiga-
tions of the catalytic conversion of esters into carbonyl
compounds with pronucleophiles, in which the py-
ridinemethoxy group functions as a base, are currently
underway. Various types of acyl transition metal alkoxo
complexes would be generated from esters by various
combinations of catalysts and directing groups, suggest-
ing a wide spectrum of catalytic reactions could be
explored.
substitution of an electron-withdrawing group, such as
an ethoxycarbonyl group. Similarly, a difference in the
steric effects was also observed in the two reactions.
Thus, adamandanecarboxylate served as a good substrate
in the cross-coupling reaction (entry 4 in Table 1), but
no reaction took place in the reactions with HCOONH4
(Table 3). Ligand substitution (46 f 47) by formate
anion, which is a weak nucleophile, is accelerated by the
resonance effect of the electron-donating group, such as
a methoxy group (Scheme 6), and/or the reductive
elimination from 47 is promoted by the electron-donating
nature of the methoxy group. On the other hand, ligand
substitution does not take place from 30 because the acyl
ligand is a strong electron-withdrawing group. In addi-
tion, decarbonylation from 30 (R ) adamantly) is sup-
pressed by its bulkiness in the case of 40g and ligand
exchange after decarbonylation cannot proceed. This
proposal is supported by the fact that this reaction did
not proceed even at 1 atm of CO under which decarbo-
nylation was suppressed. On the other hand, it is known
that alkoxo metal complexes easily undergo transmeta-
lation with organoboron compounds because of the oxo-
philicity of the boron atom, and so 30 undergoes the
transmetalation with organoboron compounds prior to
decarbonylation.
Ack n ow led gm en t. This work was supported, in
part, by grants from The Ministry of Education, Science,
Sports, and Culture and the J apan Society for the
Promotion of Science. N.C. wishes to thank to the
Tokuyama Foundation for financial support. H.T. ac-
knowledges Research Fellowships of J .S.P.S. for Young
Scientists.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and characterization data for new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O0492719
It was anticipated that aldehydes, which are formed
via the reduction of esters by HCOONH4, would be
produced initially and then undergo decarbonylation to
give hydrocarbons under the reaction conditions used
here. To examine this possibility, some selected controlled
experiments were performed. The reaction of 2-naphtha-
lenecarbaldehyde (33) under reaction conditions identical
with those in eq 7 gave naphthalene in 23% GC yield,
(32) For reviews on the decarbonylation of aldehydes, see: Baird,
M. C. The Chemistry of Acid Derivatives; Patai, S., Ed.; Wiley: New
York, 1979; pp 825-857. Colquhoun, H. M.; Thompson, D. J .; Twigg,
M. V. Carbonylation: Direct Synthesis of Carbonyl Compounds; Plenum
Press: New York and London, 1991. Tsuji, J . In Handbook of
Organopalladium Chemistry for Organic Synthesis; Negishi, E., Ed.;
J ohn Wiley & Sons: New York, 2002; pp 2643-2653.
(33) Na, Y.; Park, S.; Han, S. B.; Han, H.; Ko, S.; Chang, S. J . Am.
Chem. Soc. 2004, 126, 250.
J . Org. Chem, Vol. 69, No. 17, 2004 5621